Difference in metallic wear distribution released from commercially pure titanium compared with stainless steel plates.

INTRODUCTION: Stainless steel and commercially pure titanium are widely used materials in orthopedic implants. However, it is still being controversially discussed whether there are significant differences in tissue reaction and metallic release, which should result in a recommendation for preferred use in clinical practice. MATERIALS AND METHODS: A comparative study was performed using 14 stainless steel and 8 commercially pure titanium plates retrieved after a 12-month implantation period. To avoid contamination of the tissue with the elements under investigation, surgical instruments made of zirconium dioxide were used. The tissue samples were analyzed histologically and by inductively coupled plasma atomic emission spectrometry (ICP-AES) for accumulation of the metals Fe, Cr, Mo, Ni, and Ti in the local tissues. Implant corrosion was determined by the use of scanning electron microscopy (SEM). RESULTS: With grades 2 or higher in 9 implants, steel plates revealed a higher extent of corrosion in the SEM compared with titanium, where only one implant showed corrosion grade 2. Metal uptake of all measured ions (Fe, Cr, Mo, Ni) was significantly increased after stainless steel implantation, whereas titanium revealed only high concentrations for Ti. For the two implant materials, a different distribution of the accumulated metals was found by histological examination. Whereas specimens after steel implantation revealed a diffuse siderosis of connective tissue cells, those after titanium exhibited occasionally a focal siderosis due to implantation-associated bleeding. Neither titanium- nor stainless steel-loaded tissues revealed any signs of foreign-body reaction. CONCLUSION: We conclude from the increased release of toxic, allergic, and potentially carcinogenic ions adjacent to stainless steel that commercially pure Ti should be treated as the preferred material for osteosyntheses if a removal of the implant is not intended. However, neither material provoked a foreign-body reaction in the local tissues, thus cpTi cannot be recommend as the 'golden standard' for osteosynthesis material in general.

Surface composition analysis of failed cementless CoCr- and Ti-base-alloy total hip implants.

The surfaces of retrieved failed cementless total hip implants made of cobalt-chromium-molybdenum casting alloy and of wrought titanium 6-aluminum 4-vanadium alloy were studied with the use of scanning-electron microscopy (SEM), energy-dispersive X-ray analysis (EDX) and X-ray photoelectron spectroscopy (XPS). New implants of the same make served as controls. The XPS scans revealed a dense carbon layer on the entire analyzed specimen. The relative composition of the titanium alloy implants showed an overall agreement with the international standards for implants for surgery, and the overall surface composition did not change over the period of the implantation. However, an inhomogeneous distribution of the constituents could be demonstrated in the retrieved as well as in the new MEC-screw rings made of TiAl6V4 alloy, an implant that has been linked to a high early failure rate. In the CoCr-alloy components (Lord-screw rings) a high percentage of aluminum, mainly organized in aluminum inclusions, was found in the retrieved as well as in the new implants.

Evaluating alternative cannabis regimes.

BACKGROUND: Cannabis policy continues to be controversial in North America, Europe and Australia. AIMS: To inform this debate, we examine alternative legal regimes for controlling cannabis availability and use. METHOD: We review evidence on the effects of cannabis depenalisation in the USA, Australia and The Netherlands. We update and extend our previous (MacCoun & Reuter, 1997) empirical comparison of cannabis prevalence statistics in the USA, The Netherlands and other European nations. RESULTS: The available evidence indicates that depenalisation of the possession of small quantities of cannabis does not increase cannabis prevalence. The Dutch experience suggests that commercial promotion and sales may significantly increase cannabis prevalence. CONCLUSIONS: Alternatives to an aggressively enforced cannabis prohibition are feasible and merit serious consideration. A model of depenalised possession and personal cultivation has many of the advantages of outright legalisation with few of its risks.

[3-phase spiral CT of the liver, Value of non-contrast arterial and portal venous studies in the diagnosis of focal liver lesions]. / 3-Phasen-Spiral-CT der Leber. Stellenwert von nativer, arterieller und portalvenöser Untersuchungsserie für die Diagnostik fokaler Leberläsionen.

PURPOSE: To assess the value of noncontrast, arterial and portal venous phase of triphasic helical CT in detecting and characterising focal liver lesions. MATERIAL AND METHODS: 120 patients with focal liver disease underwent triphasic helical CT examinations with a collimation of 6.5 mm at a table feed of 6.5 mm/s. The liver scans were obtained before the administration of 120 ml of non-ionic contrast material (flow 2 or 3 ml/s), at the arterial phase, and at the portal venous phase (20 s, respectively 60 s after injection). Patients were divided into four groups according to the underlying disease and enhancement pattern. The studies were evaluated retrospectively. RESULTS: A total of 269 lesions was seen. The noncontrast phase (NCP) revealed 86% of lesions, the arterial phase (AP) 95% and the portal venous phase (PVP) 91%. In the first group of hypovascular lesions (colorectal carcinoma) all lesions (73/73) were detected in the PVP. In the second group of hypervascular lesions (breast cancer, melanoma) the combination of AP and PVP revealed 73 of 74 lesions. In the third group of patients with unknown primary and detected lesions by sonography all 89 lesions were detected with the combination of AP and PVP. In the fourth group of patients with cirrhosis 3 of 33 lesions were detected exclusively during the AP and 3 other lesions exclusively during the NCP. To make a definitive diagnosis of focal liver lesions the value of the three phases was as follows: to characterise lesions the PVP was sufficient in 62%, the combination of PVP and AP in 27%, and the combination of all three phases in 11%. CONCLUSIONS: If hypovascular lesions are suspected examination during PVP is sufficient. In cases of hypervascular lesions and lesions of unknown primary AP and PVP should be combined. Unenhanced scans are of additional diagnostic value only in patients with liver cirrhosis.

Redefining the goals of national drug policy: recommendations from a working group.

This paper discusses what the goals of national drug policy have been and suggests an alternative set of goals. The past emphasis on use reduction is found wanting. Total harm related to drugs can be viewed as the product of use and harm per use. Thus, reducing use usually serves to reduce harm. However, in some cases, use reduction programs may increase harm per use so much that they increase overall harm even as they succeed in reducing use. Hence, use reduction goals can be usefully augmented with the explicit objective of reducing the total harm created by the production, distribution, consumption, and control of drugs. Numerous programmatic recommendations flow from this approach.

Generation of a T-cell hybridoma producing a contrasuppressor factor for contact sensitivity.

C3H/HeN mice were immunized to induce contrasuppressor T-cell (Tcs) activity, splenic T cells from these mice were fused with the BW5147 thymoma, and the resulting hybridomas were tested for their ability to produce a contrasuppressor T-cell factor (TcsF). Nine TcsF-producing hybridomas were preliminarily identified by their ability to inhibit the effect of antigen-specific suppressor T-cell factor (TsF) on the adoptive transfer of contact sensitivity. One of these hybrids, AF5.C6, was cloned, the production of a contrasuppressor factor confirmed, and the high-titred TcsF produced by this cloned hybrid characterized. Hybridoma-derived TcsF is antigen-specific and specifically binds its antigen, but does not bear immunoglobulin (Ig) determinants. Thus, hybridoma-derived TcsF is serologically and functionally identical to an antigen-specific contrasuppressor factor for contact sensitivity, whose production from splenocyte cell cultures has previously been described. The generation of a hybridoma secreting a contrasuppressor factor identical to that produced by spleen cells significantly strengthens the hypothesis that the phenomenon of T-cell contrasuppression is mediated by a specific subset of cells whose activity is contrasuppressive. The further advantages of employing T-cell hybridomas for functional, biochemical and molecular genetic analyses of contrasuppression are also discussed.

Functional characterization of Tat protein from human immunodeficiency virus. Evidence that Tat links viral RNAs to nuclear matrix.

The processes of transcription and posttranscription are assumed to proceed in close association with the nuclear matrix. In this study we demonstrated that Tat, the trans-activating protein from human immunodeficiency virus type 1 (HIV-1), binds both to the TAR region of the nascent HIV mRNAs and the nuclear matrix with high affinity. Both North/Western blotting experiments and nitrocellulose binding studies revealed that Tat binds with an association constant (K alpha) of approximately 1 x 10(9) M-1 to the TAR segment of HIV RNA; binding of Tat to this sequence which is present between position 32 and 82 downstream from the TATA box was also confirmed by gel retardation assays. Binding of Tat to TAR only occurs if the loop segment in the proposed stem-loop secondary structure of HIV leader mRNA is present. Likewise, Tat binds to the nuclear matrix with a K alpha of 7.5 x 10(7) M-1. The number of binding sites has been estimated to be 2 x 10(8)/micrograms of matrix protein, corresponding to 4 x 10(3) sites/nucleus. Tat displays its bimodal function only in the presence of Zn2+ ions. In vitro transcription experiments, using HIV-1 infected nuclei, demonstrate that beyond the TAR-region HIV RNA synthesis occurs only in the presence of Tat. Present studies indicate that Tat may function as a linker by binding of nascent HIV RNAs to the nuclear matrix.

Inhibitory effect of nonviable preparations from human immunodeficiency virus 1 on inositol phospholipid metabolism.

Previously it was established [Pahwa, S., Pahwa, R., Saxinger, C., Gallo, R. C. & Good, R. A. (1985) Proc. Natl. Acad. Sci. USA 82, 8198] that nonviable preparations of human immunodeficiency virus 1 (HIV-1) abolish the proliferative response of human lymphocytes to phytohemagglutinin A. Now we describe that this effect might be, at least partially, due to an impairment of the function of phospholipase C. It was found that addition of HIV-1 preparation to lymphocytes diminished the stimulation of phosphatidylinositol phosphorylation caused by phytohemagglutinin A. Moreover, this preparation completely abolished the phytohemagglutinin-A-stimulated release of inositol trisphosphate and prevented a translocation of protein kinase C from cytosol to membranes. From this data we conclude that nonviable HIV-1 preparations inhibit the intracellular signalling pathway, leading to a reduced mitogenic response to phytohemagglutinin A, at the level of protein kinase C.

Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan.

The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that L-tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiency virus agent avarol, possibly by different mechanisms. Avarol has been shown to be able to modulate posttranscriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in L1210 mouse leukemia cells. In addition, L-tryptophan suppressed the induction of gamma-interferon mRNA production in human peripheral blood lymphocytes. At the level of DNA, L-tryptophan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids.

Inhibition of expression of natural UAG suppressor glutamine tRNA in HIV-infected human H9 cells in vitro by Avarol.

HTLV-IIIB-infected H9 cells are shown to contain a high level of the natural UAG suppressor glutamine tRNA(UmUG Gln); this tRNA has been demonstrated to be required for the synthesis of Moloney murine leukemia virus (Mo-MuLV)-encoded protease. After cultivation of HTLV-IIIB-infected H9 cells with Avarol at a concentration (1 microgram/ml), previously found to protect the cells against the cytopathic effects of HTLV-III, an almost complete inhibition of the synthesis of the tRNA(UmUG Gln) was observed. Moreover, we obtained some evidence that the processing of the HTLV-III precursor protein p53 to p24 is inhibited by Avarol in infected cells, suggesting that the compound interferes with the expression of the viral protease gene.

Induction of gamma-interferon by avarol in human peripheral blood lymphocytes.

Avarol is a cytostatic and anti-human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of gamma-interferon (IFN-gamma) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN-gamma production was detected after a 24-hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 microgram/ml. Blotting experiments using human IFN-gamma cDNA and beta-actin cDNA containing plasmids showed that in the absence of avarol no IFN-gamma transcripts were present in lymphocytes. Already after a 24-hr incubation with avarol, IFN-gamma gene induction was detected, and maximal induction was found after a 5-day incubation period. The enhanced IFN-gamma production seems to be caused by a change at the transcriptional and/or post-transcriptional level, but not during subsequent nucleocytoplasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the beta-actin gene. Our studies demonstrate that avarol displays, besides its potential anti-tumor and anti-HIV activity, a potential immunomodulating effect.